Chapter 27 - Antidepressant Actions on Glucocorticoid Receptors

Effective antidepressant treatment has been shown to resolve the hypothalamic–pituitary–adrenal (HPA) axis dysregulation implicated in pathogenesis of depression. The hyperactivity of the HPA axis in depressed patients appears to reflect an altered function of glucocorticoid receptors (GR), which play a crucial part in the feedback regulation of the axis. Evidence suggests that antidepressants exert their effect directly on GR through increasing expression, promoting translocation, and enhancing function of the receptor in the brain and other target tissues, and hence normalizing HPA axis abnormalities. This chapter focuses on the HPA axis and on the GR and describes how effective antidepressant medications restore the neuroendocrine-immune balance through modulation of the GR. Investigation of the molecular pathways underlying the effects of antidepressants on regulation of the GR function is crucial for enhancing our understanding of the therapeutic efficacy of these medications and provides mechanistic insight for developing new antidepressant agents.